Contact information
Type
Scientific
Primary contact
Prof Marianne Thoresen
ORCID ID
Contact details
School of Clinical Sciences
University of Bristol
Neonatology
St Michael's Hospital
Southwell Street
Bristol
BS2 8EG
United Kingdom
+44 (0)117 342 5607
Marianne.Thoresen@bristol.ac.uk
Additional identifiers
EudraCT number
2009-014260-19
ClinicalTrials.gov number
Protocol/serial number
Version 1.21 (as of 05/01/2011)
Study information
Scientific title
A feasibility study of adding xenon to cooling therapy in babies at high risk of brain injury following poor condition at birth
Acronym
CoolXenon
Study hypothesis
Our experimental work has shown that by adding the inert gas xenon (50%) while undergoing hypothermia treatment the % good outcome doubles (from 35% to 70%) in both small and large survival models. This is the first clinical feasibility study combining xenon inhalation with the established neuroprotective hypothermia treatment in newborn term after moderate and severe perinatal asphyxia.
Further reading:
Dingley J, Tooley J. Porter H, Thoresen M. Xenon provides short term neuroprotection in neonatal rats when administered after hypoxia-ischemia. Stroke 2006; 37(2): 501-6.
http://www.ncbi.nlm.nih.gov/pubmed/16373643
Dingley J, Hobbs C, Ferguson J, Thoresen M. Xenon/hypothermia neuroprotection regimes in spontaneously breathing neonatal rats after hypoxic-ischemic insult: respiratory and sedative effects. Anaesthesia and Analgesia 2008; 106: 916-923.
http://www.ncbi.nlm.nih.gov/pubmed/18292440
Hobbs C, Thoresen M, Tucker AM, Aquilina K, Chakkarapani E, Dingley J. Xenon and hypothermia combine additively offering long term functional and histopathological neuroprotection after neonatal hypoxia-ischemia. Stroke 2008; 39(4): 1307-13.
http://www.ncbi.nlm.nih.gov/pubmed/18309163
Chakkarapani E, Thoresen M, Hobbs C, Aquilina K, Liu X, Dingley J. A closed-circuit neonatal xenon delivery system: technical neuroprotection feasibility study in newborn pigs. Anaesthesia and Analgesia 2009; 109(2): 451-60.
http://www.ncbi.nlm.nih.gov/pubmed/19608817
Thoresen M, Hobbs C, Wood T, Chakkarapani E, Dingley J. Cooling combined with immediate or delayed Xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia. Journal of Cerebral Blood Flow and Metabolism 2009; 29(4): 707-14.
http://www.ncbi.nlm.nih.gov/pubmed/19142190
Thoresen M. Patient selection and prognostication with hypothermia treatment. Seminars in Fetal and Neonatal Medicine 2010; 15(5): 247-52
http://www.ncbi.nlm.nih.gov/pubmed/20580626
As of 01/03/2011 the target number of participants has been increased from 12 to 14
Ethics approval
North Somerset and South Bristol Research Ethics Committee approved on the 16th September 2009 (ref: 09/H0106/64)
Study design
Interventional non-randomised single centre feasibility study
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
GP practices
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Neurological; Subtopic: Neurological (all Subtopics); Disease: Nervous system disorders
Intervention
Adding xenon to the inspiratory gas of the ventilated infant using a MHRA approved closed loop xenon-delivery system. The xenon, oxygen, carbon dioxide (CO2) and nitrogen gas concentrations are controlled.
Follow up length: 42 months
Study entry: registration only
Added 01/03/2011: The duration of treatment with Xenon gas has been increased from 12 hours to 18 hours for recruits 12, 13 and 14
Intervention type
Drug
Phase
Not Applicable
Drug names
Xenon
Primary outcome measures
Physiological changes, measured within 24 hours after end treatment
Secondary outcome measures
1. Bayley III, measured at 18 or 24 months
2. MRI, measured within 14 days after treatment
Overall trial start date
28/03/2010
Overall trial end date
01/03/2013
Reason abandoned
Eligibility
Participant inclusion criteria
Infants will be eligible for xenon if the St Michael's standard inclusion criteria for cooling are met. Standard Hypothermia Treatment Criteria for 72 hours of cooling - all of criteria A, B, and C:
A: Infants greater than 36.0 weeks gestation (clinical assessment) with at least one of the following:
1. Apgar score of less than 5 at ten (10) minutes after birth
2. Continued need for resuscitation, including endotracheal or mask ventilation, at ten minutes after birth
3. Acidosis defined as either umbilical cord pH or any arterial, venous or capillary pH within 60 minutes of birth less than pH 7.00
4. Base deficit greater than or equal to 16 mmol/L in umbilical cord blood sample or any blood sample within 60 minutes of birth (arterial or venous blood)
If the infant meets criterion A then assess for neurological abnormality using criterion B and C (by trained personnel).
B: Moderate or severe encephalopathy as evidenced by:
1. Altered state of consciousness (reduced or absent responses or pathological irritability and hyper responsive
And at least one or more of the following:
2. Hypotonia
3. Abnormal reflexes including oculomotor or pupillary abnormalities
4. Absent or weak suck
5. Clinical seizures, as recorded by trained personnel
C: At least 30 minutes duration of amplitude integrated electroencephalography (aEEG) recording that shows abnormal background aEEG activity. The decision to cool is based on the worst section of the aEEG, not the best (al Naqeeb, et al, 1999) or seizures (clinical or electrical) thus meeting ONE of the following:
1. Normal background with some electrical seizure activity
2. Moderately abnormal activity (upper margin of trace greater than 10 µV and lower margin less than 5 µV)
3. Suppressed activity (upper margin of trace less than 10 µV and lower margin of trace less than 5 µV)
4. Definite seizure activity
Additional inclusion criteria for xenon:
Before being considered for additional inhaled xenon therapy via the breathing gas mixture, the infant would need to meet further additional entry criteria:
1. Intubated, ventilated, sedated, being cooled
2. Any seizures under control
3. Weight greater than 2.3 kg
4. No evidence of infection
5. Stable cardiovascular parameters - mean arterial pressure greater than 45mmHg
6. Oxygen requirement via mechanical ventilator less than 35%
7. Positive end expiratory pressure (PEEP) requirement less than 6 mmHg
8. Arterial pCO2 within the accepted range (4.5 - 6.5 kPa)
9. Postnatal age less than 18 hours, either sex
10. Major congenital abnormalities, imperforate anus and congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Added 01/03/2011: 14 (12 at time of registration)
Participant exclusion criteria
1. Infants expected to be greater than 12 hours of age at the time of starting cooling treatment
2. Futility; where prognosis is considered to be hopeless, e.g. no cardiac output for 20 minutes
3. Failure to meet the additional inclusion criteria for xenon
Recruitment start date
28/03/2010
Recruitment end date
01/03/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
School of Clinical Sciences
Bristol
BS2 8EG
United Kingdom
Sponsor information
Organisation
University Hospitals Bristol NHS Foundation Trust (UK)
Sponsor details
Research and Development
Upper Maudlin Street
Bristol
BS2 8AE
United Kingdom
+44 (0)117 342 0233
research@uhbristol.nhs.uk
Sponsor type
Government
Website
Funders
Funder type
Charity
Funder name
Sparks (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary